System and Method for Conditioning a Diaphragm of a Patient

ABSTRACT

A method of conditioning a diaphragm of a patient is provided. The method can include the steps of implanting an electrode adjacent a target site in the diaphragm of the patient and operating the electrode to deliver a sufficient amount of electrical stimulation to the target site in the diaphragm of the patient to cause the diaphragm to contract.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of pending U.S. application Ser. No.10/897,685, filed Jul. 23, 2004, which claims priority to U.S.Provisional Application No. 60/481,124 filed Jul. 23, 2003, which isherein incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

A patient may need respiratory assistance as a result of disease andinjuries of various kinds. The need can be direct, especially when theinjury or illness afflicts the patient's respiratory system. The needcan also be indirect, e.g., during anesthesia and some intensive care.The respiratory assistance can encompass everything from facilitatingspontaneous breathing to total control of breathing. Typically, amechanical ventilator is employed to provide the breathing assistance.

One potential problem occurring in long-term controlled respiration isthat the patient's own respiratory musculature becomes weakened. In manyinstances, the patient then loses the ability to breathe spontaneouslyafter the true need for assisted respiration has been eliminated.Weaning the patient off the ventilator then takes longer. This causes acost increase to the society in the form of longer treatment durationtimes and, more important, increases the discomfort and risk ofsecondary disease for the patient.

Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's Diseaseor Motor Neuron Disease) is a progressive neurodegenerative disease ofunknown cause. Approximately 1.4 individuals per 100,000 develop ALSannually and the peak incidence is between the ages of 55 and 75. Theexact etiology of ALS is unknown although many potential causes havebeen proposed including exposure to neurotoxic agents, genetic orautoimmune disease, deficiencies of nerve growth factors, and viralinfection. The typical clinical presentation is that of an individualwith gradually progressive asymmetric weakness associated withhyperreflexia, muscle atrophy and fasciculations. Typically patientshave difficulty with walking, balance, picking up objects, andeventually any limb muscle movement. The diagnosis of ALS is made on thebasis of the history, a physical examination revealing upper and lowermotor neuron signs, and electromyography demonstrating signs ofdisseminated active denervation and true reinnervation.

One effect of progressive neuromuscular weakness in patients with ALS isthe effect on respiration. Although ALS has no direct effect on thelung, it has devastating effects on mechanical function of therespiratory system. ALS affects all of the major respiratory musclegroups: upper airway muscles, expiratory muscles, and inspiratorymuscles. Therefore, all patients with ALS are at significant risk forrespiratory complications. Progressive inspiratory muscle weakness inALS inevitably leads to carbon dioxide retention, inability to clearsecretions and hypercarbic respiratory failure, the major cause of deathin ALS. At some point, ALS involves the respiratory muscles so severelythat bulbar paresis is combined with severe expiratory and inspiratorymuscle weakness and invasive ventilation becomes the only option forsurvival.

BRIEF DESCRIPTION OF THE DRAWINGS

It will be appreciated that illustrated boundaries of elements (e.g.,boxes, groups of boxes, or other shapes) in the figures represent oneexample of the boundaries. One of ordinary skill in the art willappreciate that one element may be designed as multiple elements or thatmultiple elements may be designed as one element. An element shown as aninternal component of another element may be implemented as an externalcomponent and vice versa.

FIG. 1 is a schematic diagram of one embodiment of a system 100 forconditioning a diaphragm of a patient.

FIG. 2 is a plan view of one embodiment of an intramuscular electrode.

FIG. 3 is a diagram of the anatomy of the diaphragm from the view pointof the abdominal surface.

FIG. 4 is a schematic diagram of another embodiment of a system 400 forconditioning a diaphragm of a patient.

FIG. 5 is a schematic diagram of one embodiment of a methodology 500 forconditioning the diaphragm of a patient.

DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS

The following includes definitions of selected terms used throughout thedisclosure. The definitions include examples of various embodimentsand/or forms of components that fall within the scope of a term and thatmay be used for implementation. Of course, the examples are not intendedto be limiting and other embodiments may be implemented. Both singularand plural forms of all terms fall within each meaning:

“Patient,” as used herein, includes but is not limited to any livingcreature, i.e. human or animal.

“Signal”, as used herein, includes but is not limited to one or moreelectrical signals, AC or DC, analog or digital signals, one or morecomputer or processor instructions, or other means that can be received,transmitted, and/or detected.

“Software”, as used herein, includes but is not limited to one or morecomputer readable and/or executable instructions that cause a computeror other electronic device to perform functions, actions, and/or behavein a desired manner. The instructions may be embodied in various formssuch as objects, routines, algorithms, modules or programs includingseparate applications or code from dynamically linked libraries.Software may also be implemented in various forms such as a stand-aloneprogram, a function call, a servlet, an applet, instructions stored in amemory, part of an operating system or other type of executableinstructions. It will be appreciated by one of ordinary skill in the artthat the form of software may be dependent on, for example, requirementsof a desired application, the environment it runs on, and/or the desiresof a designer/programmer or the like. It will also be appreciated thatcomputer-readable and/or executable instructions can be located in onelogic and/or distributed between two or more communicating,co-operating, and/or parallel processing logics and thus can be loadedand/or executed in serial, parallel, massively parallel and othermanners.

A system and method is provided for electrically stimulating thediaphragm of a patient to condition the diaphragm of the patient. Asused herein, the term “condition” can mean maintaining the strength of,strengthening, building the fatigue resistance of the diaphragm of thepatient, or changing other contractile properties of the diaphragmmuscle fibers. Although not wishing to be bound by theory, electricalstimulation can also have one or more of the following effects that areintended to be included in the meaning of the term “condition”: 1)eliciting muscle fiber type conversion (from fast twitch, rapidlyfatiguing, type I fibers to slow twitch, slowly fatiguing type IIfibers); 2) increasing muscle mass (through reversal of disuse atrophy);3) changing the contractile properties of the muscle by stimulatingthrough the muscle's range of motion (thereby reducing any shortening offibers and/or spasticity), and 4) even potentially having an effect ofcollateral sprouting of adjacent nerve fibers to innervate muscle thathas lost its innervation through damage to the phrenic nerve or lowermotor neuron.

To condition the diaphragm of the patient, a sufficient amount ofelectrical stimulation can be continuously or periodically applied toone or more sites in the diaphragm to achieve at least one of theeffects described above.

Illustrated in FIG. 1 is one embodiment of a system 100 for electricallystimulating the diaphragm of a patient to condition the diaphragm of thepatient. The system 100 can be used to treat patients having ALS or anyother disorder that attacks the respiratory musculature. Generally, thesystem 100 can include an electrical signal generator 110, electrodes120 implanted into the diaphragm of the patient to apply electricalstimulation to the diaphragm of the patient. Electrical signal generator110 is connected to electrodes 120 by stimulus cable 130 and apercutaneous connector 150 as shown.

In one embodiment, the electrical signal generator 110 can be configuredto generate pulses and/or signals that may take the form of sinusoidal,stepped, trapezoidal waveforms or other relatively continuous signals.The electric signal generator 110 can include one or more channels thatcan independently control the amplitude, frequency, timing and pulsewidth of the corresponding electrodes connected thereto.

In one embodiment, the electrical signal generator 110 can be anexternal signal generator that is electrically connected to or inelectrical communication with the electrodes 120. One example of asuitable electrical signal generator is the NeuRx RA/4 stimulator thatis manufactured by Synapse Biomedical, Inc. of Oberlin, Ohio. The NeuRxRA/4 stimulator is a four-channel device with independent parameterprogrammability. It will be appreciated that since the NeuRx RA/4stimulator has four channels, it has the capability to independentlycontrol up to four electrodes. In an alternative embodiment, theelectrical signal generator 110 can be an implantable signal generator.One suitable example of a fully implanted signal generator is the “ITRELII” electrical signal generator available from Medtronic, Inc. ofMinneapolis, Minn. One example of a partially implanted radio-frequencysignal generator system is the “XTREL” system also available fromMedtronic, Inc.

As stated above, the system 100 can include electrodes 120 implanted inthe diaphragm of the patient to provide electrical stimulation to thediaphragm. Although FIG. 1 illustrates utilization of two electrodes inthe system 100, it will be appreciated that more than two electrodes orone electrode can be used to provide sufficient electrical stimulation.

Illustrated in FIG. 2 is one embodiment of an intramuscular electrode120 that can be implanted into a patient. For example, the electrode 120can be an intramuscular electrode that is configured to be implantedinto the muscle tissue of the patient. In one embodiment, theintramuscular electrode 120 can serve as a cathode.

One example of a suitable intramuscular electrode is the Petersonintramuscular electrode (P/N 21-0002) manufactured by SynapseBiomedical, Inc. of Oberlin, Ohio, which is the electrode illustrated inFIG. 2. In one configuration, the Peterson intramuscular electrode is adouble helix wound from multistrand stainless steel wire insulated influoropolymer with a polypropylene core and barb. The electrode can havea barb 210 that is flattened and bent back along the line of theelectrode, a polypropylene skirt 220, and a deinsulated coil 230 underthe skirt 220. The electrode lead can terminate with a stainless steelpin 240 crimped to the de-insulated end and back-filled with siliconeadhesive for strain relief. Obviously, it will be appreciated that theintramuscular electrode can take the form of other shapes, sizes, andconfigurations, and can be made of other materials suitable forimplantation into a patient.

In one embodiment, the electrodes 120 can be implanted into target sitesin the diaphragm of the patient. For example, the electrodes 120 can beimplanted into or adjacent the phrenic nerve motor points of thediaphragm (i.e., where the phrenic nerve enters the diaphragm) of thepatient. The phrenic nerve motor points of the diaphragm are locationsin the diaphragm that provide the greatest muscle fiber recruitment inresponse to an applied stimulation.

Illustrated in FIG. 3 is a cross-section of an exemplary diaphragm andthe locations of the motor points in each hemidiaphragm. The phrenicnerve motor points of the diaphragm can be advantageous sites to implantthe electrodes because electrical stimulation of these sites can producea diaphragmatic contraction. It will be appreciated that the diaphragmcan be defined in terms of left and right hemidiaphragms and that one ormore electrodes can be implanted into or adjacent the phrenic nervemotor points of only the left hemidiaphragm, only the righthemidiaphragm, or both left and right hemidiaphragm.

In one embodiment, an electrode 120 can be implanted into or adjacentthe phrenic nerve motor points of each hemidiaphragm and an additionalelectrode can be implanted in each hemidiaphragm for one or more of thefollowing reasons: 1) to backup the primary electrode (i.e., theelectrode implanted adjacent the phrenic nerve motor point); 2) to bepositioned near the primary electrode to gain higher output if thephrenic nerve motor point is imprecisely located; or 3) to be positionednear the primary electrode to allow for surgical error in placement nearthe phrenic nerve motor point. Alternatively, if the phrenic nerve motorpoint is on the central tendon, one or more electrodes can be positionednear branches of the phrenic nerve.

In one embodiment, the system 100 can include an indifferent electrode140. The indifferent electrode 140 can be similar to the intramuscularelectrodes 120 shown and described above, except that it has a shorterde-insulated tip and does not have a barb at one end. In one embodiment,the indifferent electrode can be used as a common anode that can providea return for the electrical charge from the electrodes 120. One suitableexample of an indifferent electrode is PN 21-0004 manufactured bySynapse Biomedical, Inc. It will be appreciated that other indifferentelectrodes can take the form of other shapes, sizes, and configurations,and can be made of other materials suitable for implantation into apatient or placed on the skin surface.

In one embodiment, the indifferent electrode 140 can be implanted in thesubcutaneous tissue adjacent the diaphragm of the patient.Alternatively, the indifferent electrode 140 can be implanted in otherareas such as integral to an implanted pulse generator or placed on theskin surface.

In one embodiment, the electric signal generator 110 can supply theelectrodes 120 with an electrical signal that serves as electricalstimulation. For example, the electrical signal can be a capacitivelycoupled, charge balanced, biphasic, constant current waveform withadjustable parameters as shown below in Table 1. It will be appreciatedthat the electrical signal can take the form of other waveforms forelectrical stimulation such as monophasic or rectangular biphasic.

TABLE 1 Parameter Range Stimulation Interleave Rate 1-100 Trigger Delay(from inspiration) 1.0-4.0 s Stimulation Time 0.8-1.5 s Output PulsePeriod 20-250 ms Pulse Width Modulation Count 0-10  Cathodic CurrentAmplitude 5-25 mA Cathodic Current Pulse Width 20-200 μs Voltage 0-65 VPulse Frequency 10-20 Hz

In one embodiment, the electrical stimulation can be delivered to thediaphragm of the patient continuously or periodically. For example, theelectrical stimulation can be delivered to the diaphragm of the patientat specified intervals per day (e.g., 5-6 sessions per day) for acertain period of time per interval (e.g., 5 minutes per sessiontotaling about 25-30 minutes per day). Obviously, the electricalstimulation can be delivered at different intervals depending on theneeds of a particular patient.

In one embodiment, the electrodes 120 can be implanted into thediaphragm of the patient using a laproscopic procedure. One suitabledevice that can be used to implant the electrodes 120 into the patient'sdiaphragm is the electrode delivery instrument shown and described inU.S. Pat. No. 5,797,923, which is herein incorporated by reference inits entirety. In another embodiment, the electrodes 120 can be implantedinto the diaphragm of the patient using an open surgical technique andplacement with a hypodermic needle.

To locate the phrenic nerve motor points in each hemidiaphragm of thepatient, a mapping procedure can be performed on the patient. In onemapping procedure, a test electrode and mapping software can be used tomap the response of stimulus in each hemidiaphragm. The electrodeincludes a metal ring surrounded by tubing. The tubing extends from themetal ring a surgery-room vacuum port. The tubing is also connected to apressure transducer for measurement of intra-abdominal pressure duringthe mapping procedure. To begin the procedure, the electrode is placedinto contact with the diaphragm muscle tissue and held against themuscle tissue with suction. When the electrode is introduced into theperitoneal space, the tubing and metal ring are enclosed within acannula. When a desired test site has been identified, a standardlaparoscopic dissector is used to position and temporarily hold theelectrode against the muscle tissue until the suction has been turnedon. Electrical stimulation (e.g., stimulus amplitude of 20 mA and pulseduration of 100 μs) is delivered through the electrode resulting indiaphragm contraction. The magnitude of the evoked muscle response andvisual confirmation of the contraction are recorded and noted,respectively. Also, the resultant change in pressure of the abdominalcavity is recorded. The suction can then be turned off, the electrodemoved to a new test site, and the process can be repeated. With thisinformation, the diaphragm of the patient is methodically mapped on agrid pattern (e.g., overlayed on the laparoscopic monitor).

The magnitude of the evoked muscle response and the resultant change inpressure of the abdominal cavity can then be used to identify theoptimal electrode implant site of each hemidiaphragm. The optimal site,which is typically referred to as a phrenic nerve motor point of thehemidiaphragm, is chosen as the site that elicits a diffuse contractionand the greatest magnitude of pressure change. Although one mappingprocedure has been described in detail above, it will be appreciatedthat other mapping procedures can be used to identify the phrenic nervemotor points in the diaphragm of the patient.

Illustrated in FIG. 4 is another embodiment of a system 400 forconditioning the diaphragm of a patient. The system 400 is similar tothe system 100 shown in FIG. 1 and described above, except that thesystem 400 is used in conjunction with a mechanical ventilator 410. Thesystem 400 can be applicable to patients with acute ventilatory needs byproviding mechanical ventilation to the patient along with diaphragmelectrical stimulation to condition the diaphragm of the patient. Insuch system, the mechanical ventilator would provide the gas exchangerequired for patient support, while the diaphragm electrical stimulationcould be used to condition the diaphragm.

In one embodiment, the system 400 can further include a flow sensor 420provided along the ventilation breathing circuit (i.e., between themechanical ventilator 410 and the upper airway of the patient). The flowsensor 420 can be used to sense inspiratory or expiratory air flow inthe ventilator circuit.

In one embodiment, the system 400 can include a stimulation apparatus430 that can include an electrical signal generator 110 (similar to theone described above) and a breathing sensor and control circuit 440 thatis in electrical communication with the electrical signal generator 110and the flow sensor 420. The breathing sensor and control circuit 440can be configured to detect certain breathing attributes of the patient(e.g., the inspiration phase of a breath, the duration of theinspiration phase, the exhalation phase of a breath, the duration of theexhalation phase, tidal volume, and/or flow rate), convert theseattributes to signals, and communicate these signals to the electricalsignal generator 110.

Optionally, the system 400 can include a pressure gauge (not shown) andgas meter (not shown). These can be provided along the ventilatorbreathing circuit to measure the pressure and gas-related parameters ofthe patient's breathing, respectively. Also, a physiological measurementunit can be connected to the patient to measure certain physiologicalparameters such as blood pressure, blood values, body temperature, etc.

In one embodiment, electrical stimulation of the diaphragm can besynchronized with attempts at breathing or breathing made by the patient(e.g., on the patient's own or by the mechanical ventilator). Forexample, electrical stimulation can be triggered following theinspiration phase of the breath (i.e., during exhalation) to maximizethe contraction during the period when the diaphragm is at its longestlength. This could be beneficial to a patient with injuries to orblockages in her/his nerve conduction system between the respiratorycenter and the respiratory musculature. It will be appreciated thatelectrical stimulation of the diaphragm of the patient may not besynchronized with attempts at breathing or breathing made by the patientand, thus, can be applied during any portion of a breath.

By applying electrical stimulation to the diaphragm periodically or atspecified intervals, weakening of the diaphragm can be reduced. When thecondition of the patient improves and he/she makes sporadic attempts tobreathe naturally, adaptation to these attempts can be made incombination with intensified muscle stimulation. This can increaseexercise of the diaphragm and prepare the patient for the time when thepatient starts taking over an increasing part of the breathing.

One possible advantage of periodically delivering electrical stimulationto the patient's diaphragm to condition the diaphragm of the patientwhile the patient is using a mechanical ventilator is that thedependence of the patient on the mechanical ventilator can end sooner.For example, electrical stimulation of the diaphragm while the patientis breathing using a mechanical ventilator can help wean the patient offthe mechanical ventilator by reversing the disuse atrophy of thediaphragm, thereby providing fatigue resistance and strength. Initially,patients may only be able to tolerate electrical stimulation of thediaphragm for a short period of time due to rapid muscle fatigue and lowdiaphragm strength resulting in low tidal volumes. Over a period ofweeks, the diaphragm can build endurance and strength and patients maybe able to tolerate electrical stimulation of the diaphragm for longerdurations until they are able to achieve full-time electricalstimulation. This can mean that the duration of hospital treatment canbe greatly reduced. Moreover, it may be possible to reduce costs andtreat more patients at hospitals when treatment durations are reduced.

Illustrated in FIG. 5 is one embodiment of a methodology 500 associatedwith conditioning the diaphragm of a patient. The illustrated elementsdenote “processing blocks” and represent computer software instructionsor groups of instructions that cause a computer or processor to performan action(s) and/or to make decisions. Alternatively, the processingblocks may represent functions and/or actions performed by functionallyequivalent circuits such as an analog circuit, a digital signalprocessor circuit, an application specific integrated circuit (ASIC), orother logic device. The diagram, as well as the other illustrateddiagrams, does not depict syntax of any particular programming language.Rather, the diagram illustrates functional information one skilled inthe art could use to fabricate circuits, generate computer software, oruse a combination of hardware and software to perform the illustratedprocessing. It will be appreciated that electronic and softwareapplications may involve dynamic and flexible processes such that theillustrated blocks can be performed in other sequences different thanthe one shown and/or blocks may be combined or, separated into multiplecomponents. They may also be implemented using various programmingapproaches such as machine language, procedural, object oriented and/orartificial intelligence techniques. The foregoing applies to allmethodologies described herein.

As shown in FIG. 5, the method 500 includes implanting an electrodeadjacent a target site in the diaphragm of the patient (block 510). Oncethe electrode has been implanted, the electrode can be operated todeliver a sufficient amount of electrical stimulation to the target sitein the diaphragm of the patient to cause the diaphragm to contract(block 520). The electrical stimulation can be delivered periodically tocause periodic contractions of the diaphragm and thereby condition thediaphragm.

To the extent that the term “includes” or “including” is used in thespecification or the claims, it is intended to be inclusive in a mannersimilar to the term “comprising” as that term is interpreted whenemployed as a transitional word in a claim. Furthermore, to the extentthat the term “or” is employed (e.g., A or B) it is intended to mean “Aor B or both”. When the applicants intend to indicate “only A or B butnot both” then the term “only A or B but not both” will be employed.Thus, use of the term “or” herein is the inclusive, and not theexclusive use. See, Bryan A. Garner, A Dictionary of Modem Legal Usage624 (2d. Ed. 1995). Also, to the extent that the terms “in” or “into”are used in the specification or the claims, it is intended toadditionally mean “on” or “onto.” Furthermore, to the extent the term“connect” is used in the specification or claims, it is intended to meannot only “directly connected to,” but also “indirectly connected to”such as connected through another component or components.

While the present invention has been illustrated by the description ofembodiments thereof, and while the embodiments have been described inconsiderable detail, it is not the intention of the applicants torestrict or in any way limit the scope of the appended claims to suchdetail. Additional advantages and modifications will readily appear tothose skilled in the art. Therefore, the invention, in its broaderaspects, is not limited to the specific details, the representativeapparatus, and illustrative examples shown and described. Accordingly,departures may be made from such details without departing from thespirit or scope of the applicant's general inventive concept.

What is claimed is:
 1. A method of weaning a patient off of aventilator, the method comprising the steps of: electrically stimulatinga target site in a diaphragm of the patient with implanted electrodeswhile the patient is breathing using the ventilator; and elicitingdiaphragm muscle fiber type conversion from fast twitch to slow twitchfibers.
 2. The method of claim 1 further comprising synchronizingelectrical stimulation with patient breaths.
 3. The method of claim 1wherein electrically stimulating comprises electrically stimulating witha trigger delay from inspiration of 1.0 seconds to 4.0 seconds.
 4. Themethod of claim 1 further comprising detecting duration of inspiration.5. The method of claim 1 further comprising detecting exhalation.
 6. Themethod of claim 5 further comprising electrically stimulating the targetsite during exhalation.
 7. The method of claim 1 further comprisingdetecting duration of exhalation.
 8. The method of claim 1 furthercomprising detecting tidal volume.
 9. The method of claim 1 furthercomprising detecting breath flow rate.
 10. The method of claim 1 furthercomprising synchronizing electrical stimulation with breathing attemptsby the patient.
 11. The method of claim 1 further comprisingsynchronizing electrical stimulation with a ventilator supplied breath.12. The method of claim 1 wherein electrically stimulating comprisesstimulating for a stimulation between from 0.8 seconds to 1.5 seconds.13. The method of claim 1 wherein electrically stimulating comprisesstimulating with an output pulse period of 20 msec to 250 msec.
 14. Themethod of claim 1 wherein electrically stimulating comprises stimulatingwith a pulse width modulation count of 0-10.
 15. The method of claim 1wherein electrically stimulating comprises stimulating with a cathodiccurrent amplitude of 5 mA to 25 mA.
 16. The method of claim 1 whereinelectrically stimulating comprises stimulating with a cathodic currentpulse width of 20 μsec to 200 μsec.
 17. The method of claim 1 whereinelectrically stimulating comprises stimulating with a voltage less thanor equal to 65 V.
 18. The method of claim 1 wherein electricallystimulating comprises stimulating with a pulse frequency of 10-20 Hz.19. The method of claim 1 further comprising increasing electricalstimulation duration to achieve full-time electrical stimulation.